Imaging of myocardial infarction using ultrasmall superparamagnetic iron oxide nanoparticles: a human study using a multi-parametric cardiovascular magnetic resonance imaging approach

Yılmaz, Ali; Dengler, Michael A.; Kuip, Heiko van der; Yıldız, Hatice; Rösch, Sabine; Klumpp, Siegfried; Klingel, Karin; Kandolf, Reinhard; Helluy, Xavier; Hiller, K. H.; Jakob, Peter M.; Sechtem, Udo

doi:10.1093/eurheartj/ehs366

Cited by 130 publications

(97 citation statements)

References 27 publications

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“…23 Ferucarbotran and ferumoxides, approved for MRI in the past, were similarly withdrawn from the market. To fulfil the clinical need, the intravenous iron replacement agent ferumoxytol (Feraheme/Rienso, 17-30 nm particles coated with a low-molecular-weight semisynthetic carboxylated polymer) was used as a contrast agent to characterize the myocardial infarct pathology 24,25 and to differentiate simple steatosis from NASH. 26 It must be noted, however, that the required concentrations of ferumoxytol were very high, 4-7.2 mg Fe/kg body weight in myocardial infarct 24,25 and 3.6 mg/kg in patients with liver disease.…”

Section: Introductionmentioning

confidence: 99%

“…To fulfil the clinical need, the intravenous iron replacement agent ferumoxytol (Feraheme/Rienso, 17-30 nm particles coated with a low-molecular-weight semisynthetic carboxylated polymer) was used as a contrast agent to characterize the myocardial infarct pathology 24,25 and to differentiate simple steatosis from NASH. 26 It must be noted, however, that the required concentrations of ferumoxytol were very high, 4-7.2 mg Fe/kg body weight in myocardial infarct 24,25 and 3.6 mg/kg in patients with liver disease. 26 In the light of the fact that this agent, indicated only for therapy of iron deficiency anemia in patients with chronic renal failure, has, in 2015, received the FDA's strongest type of warning due to the serious risk of potentially fatal anaphylactic reactions upon administration, the use of ferumoxytol for imaging may pose an enormous risk to patients, and underscores the need of a safe iron oxide-based contrast agent.…”

Section: Introductionmentioning

confidence: 99%

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Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

Unterweger

Janko

Schwarz

et al. 2017

IJN

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Iron oxide-based contrast agents have been in clinical use for magnetic resonance imaging (MRI) of lymph nodes, liver, intestines, and the cardiovascular system. Superparamagnetic iron oxide nanoparticles (SPIONs) have high potential as a contrast agent for MRI, but no intravenous iron oxide-containing agents are currently approved for clinical imaging. The aim of our work was to analyze the hemocompatibility and immuno-safety of a new type of dextran-coated SPIONs (SPIONdex) and to characterize these nanoparticles with ultra-high-field MRI. Key parameters related to nanoparticle hemocompatibility and immuno-safety were investigated in vitro and ex vivo. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we analyzed complement activation-related pseudoallergy (CARPA) upon intravenous administration of SPIONdex in a pig model. Furthermore, the size-tunability of SPIONdex and the effects of size reduction on their biocompatibility were investigated. In vitro, SPIONdex did not induce hemolysis, complement or platelet activation, plasma coagulation, or leukocyte procoagulant activity, and had no relevant effect on endothelial cell viability or endothelial–monocytic cell interactions. Furthermore, SPIONdex did not induce CARPA even upon intravenous administration of 5 mg Fe/kg in pigs. Upon SPIONdex administration in mice, decreased liver signal intensity was observed after 15 minutes and was still detectable 24 h later. In addition, by changing synthesis parameters, a reduction in particle size <30 nm was achieved, without affecting their hemo- and biocompatibility. Our findings suggest that due to their excellent biocompatibility, safety upon intravenous administration and size-tunability, SPIONdex particles may represent a suitable candidate for a new-generation MRI contrast agent.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

Unterweger

Janko

Schwarz

et al. 2017

IJN

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“…Their additional and unique diagnostic value was already proven in the settings of AMI, acute myocarditis, and acute cardiac transplant rejection in both animal models and human trials (Figures 4 and 5). 3,4,20,71,72 Hence, the use of ION-based CA can be easily implemented in existing CMR protocols. To increase their specificity, IONs can be functionalized to bind certain target structures, as shown for early cardiomyocyte apoptosis in rats, for instance.…”

Section: Promising Future Approaches In Iron Oxide-based Diagnosis Anmentioning

confidence: 99%

“…This characteristic was already shown in clinical trials for myocardial infarction, aortic aneurysms, and carotid plaques. 3,4,50,51 Furthermore, imaging of iron-laden leukocytes during pathologies such as atherosclerosis, stroke, and various types of cancer is a promising field of current preclinical research, as recently reviewed elsewhere. 20 IONs have a high sensitivity in MRI, as concentrations in the nanomolar range can be detected and visualized.…”

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confidence: 99%

Remote magnetic targeting of iron oxide nanoparticles for cardiovascular diagnosis and therapeutic drug delivery: where are we now?

Bietenbeck¹,

Florian²,

Faber³

et al. 2016

IJN

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Magnetic resonance imaging (MRI) allows for an accurate assessment of both functional and structural cardiac parameters, and thereby appropriate diagnosis and validation of cardiovascular diseases. The diagnostic yield of cardiovascular MRI examinations is often increased by the use of contrast agents that are almost exclusively based on gadolinium compounds. Another clinically approved contrast medium is composed of superparamagnetic iron oxide nanoparticles (IONs). These particles may expand the field of contrast-enhanced cardiovascular MRI as recently shown in clinical studies focusing on acute myocardial infarction (AMI) and atherosclerosis. Furthermore, IONs open up new research opportunities such as remote magnetic drug targeting (MDT). The approach of MDT relies on the coupling of bioactive molecules and magnetic nanoparticles to form an injectable complex. This complex, in turn, can be attracted to and retained at a desired target inside the body with the help of applied magnetic fields. In comparison to common systemic drug applications, MDT techniques promise both higher concentrations at the target site and lower concentrations elsewhere in the body. Moreover, concurrent or subsequent MRI can be used for noninvasive monitoring of drug distribution and successful delivery to the desired organ in vivo. This review does not only illustrate the basic conceptual and biophysical principles of IONs, but also focuses on new research activities and achievements in the cardiovascular field, mainly in the management of AMI. Based on the presentation of successful MDT applications in preclinical models of AMI, novel approaches and the translational potential of MDT are discussed.

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“…Because of the T 2 * decay time, the particles create signal loss that can be visualized and quantified on MR imaging [44]. Investigators found that iron oxide particles were specifically taken up only by activated macrophages, but not by undifferentiated monocytes.…”

Section: Journal Of Advances In Radiology and Medical Imagingmentioning

confidence: 99%

Potentials, Limitations and Future Directions of MR Contrast Media in Ablation Therapies

Saeed¹,

Liang²,

Hetts³

et al. 2016

Journal of Advances in Radiology and Medical Imaging

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Imaging of myocardial infarction using ultrasmall superparamagnetic iron oxide nanoparticles: a human study using a multi-parametric cardiovascular magnetic resonance imaging approach

Cited by 130 publications

References 27 publications

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

Remote magnetic targeting of iron oxide nanoparticles for cardiovascular diagnosis and therapeutic drug delivery: where are we now?

Potentials, Limitations and Future Directions of MR Contrast Media in Ablation Therapies

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